Immunohistochemical expression of ephrin receptors in neuroendocrine neoplasms: a case-series of gastroenteropancreatic neuroendocrine neoplasms and a systematic review of the literature.

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM Endocrine Pub Date : 2024-10-19 DOI:10.1007/s12020-024-04079-6

Krystallenia I Alexandraki, Eirini Papadimitriou, Ariadni Spyroglou, Angeliki Karapanagioti, Ioanna Antonopoulou, Irini Theohari, Odysseas Violetis, Georgios C Sotiropoulos, Stamatios Theocharis, Gregory A Kaltsas

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Abstract

Purpose: Erythropoietin-producing hepatocellular (EPH) receptors are the largest known family of tyrosine kinases receptors (TKR) in humans, implicated in cell proliferation, adhesion, migration, tumor angiogenesis, invasion and metastasis. The aim of the present study is to assess the expression of EPHs in neuroendocrine neoplasms (NENs).

Methods: Immunohistochemical staining of specimens of 30 patients with gastroenteropancreatic and lung NENs was performed for EPH-A1, EPH-A2, EPH-A4, EPH-A5 protein expression, in addition to ki-67 multiplication index and programmed death-ligand 1. Additionally, we performed a systematic review of the available literature in three different databases reporting on the expression of EPH in all neuroendocrine neoplasms.

Results: Positive expression was seen in 16/19 (84%) specimens for EPH-A1, 15/23 (65%) for EPH-A2, 21/24 (88%) for EPH-A4, 24/26 (92%) for EPH-A5. EPH-A1 was expressed in 9/9 pancreatic, 3/4 small intestine, but not in one lung NEN, EPH-A2 in 5/10 pancreatic, 3/4 small intestine and lung, and in one of each of gastric, appendix, colorectal, and cervical NENs, respectively. EPH-A4 showed positive expression in 9/11 pancreatic, 4/4 small intestine, 3/3 lung specimens and EPH-A5 in 10/11, 4/4 and 4/4, respectively. Data retrieved from the systematic review of the literature in combination with the data from the present study are suggestive of a frequent EPH expression in pituitary, thyroid, lung and gastroenteropancreatic NENs, yet, with varying expressions of the single receptor subtypes.

Conclusion: EPHs may have a role in NEN tumorigenesis, prognosis as well as a role in the evolving molecular-targeted therapies.

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神经内分泌肿瘤中ephrin受体的免疫组化表达：胃肠胰神经内分泌肿瘤病例系列和文献系统回顾。

目的：促红细胞生成素肝细胞（EPH）受体是人类已知的最大的酪氨酸激酶受体（TKR）家族，与细胞增殖、粘附、迁移、肿瘤血管生成、侵袭和转移有关。本研究旨在评估 EPHs 在神经内分泌肿瘤（NENs）中的表达情况：方法：对30例胃肠胰腺和肺部神经内分泌肿瘤患者的标本进行免疫组化染色，检测EPH-A1、EPH-A2、EPH-A4、EPH-A5蛋白的表达，以及ki-67增殖指数和程序性死亡配体1。此外，我们还对三个不同数据库中有关EPH在所有神经内分泌肿瘤中表达的现有文献进行了系统性回顾：EPH-A1在16/19（84%）份标本中阳性表达，EPH-A2在15/23（65%）份标本中阳性表达，EPH-A4在21/24（88%）份标本中阳性表达，EPH-A5在24/26（92%）份标本中阳性表达。EPH-A1 在 9/9 例胰腺癌、3/4 例小肠癌中表达，但在 1 例肺癌中没有表达；EPH-A2 分别在 5/10 例胰腺癌、3/4 例小肠癌和肺癌中表达，在胃癌、阑尾癌、结肠直肠癌和宫颈癌中各有 1 例表达。EPH-A4在9/11例胰腺标本、4/4例小肠标本和3/3例肺部标本中显示阳性表达，EPH-A5分别在10/11例、4/4例和4/4例标本中显示阳性表达。从系统性文献回顾中检索到的数据与本研究的数据相结合，表明EPH在垂体、甲状腺、肺和胃肠胰腺念珠菌病中表达频繁，但单一受体亚型的表达各不相同：结论：EPH可能在NEN肿瘤发生、预后以及不断发展的分子靶向疗法中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.